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New PTH Signals Mediating Bone Anabolism

  • Molecular Biology of Skeletal Development (T Bellido, Section Editor)
  • Published:
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Abstract

Purpose of Review

Because of its clinical relevance, extensive work has been performed to uncover the signaling pathways modulated by parathyroid hormone (PTH). This review focuses on the recent identification of novel effectors of the anabolic effect of PTH in bone.

Recent Findings

PTH-induced activation of PKA leads to inactivation of SIK2 and nuclear translocation of HDAC4/5. This inhibits MEF2C-dependent Sost expression. However, the phenotypic characterization of the HDAC4/5 double knockout mice shows normal anabolic response to intermittent PTH, supporting the notion that HDAC/Sost-independent mechanisms must exist. Lrp6 and a member of the Usp gene family have been identified as novel targets of the transcriptional coregulator Nascent polypeptide-associated complex And Coregulator alpha (αNAC) downstream from PTH activation. We propose that the αNAC cascade is involved in the transmission of the anabolic PTH signal.

Summary

Further deciphering the signaling pathways transducing the anabolic effects of PTH will allow to develop novel therapeutically relevant molecules.

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Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

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Acknowledgements

Work from the authors’ laboratory is supported by CIHR grant MOP-119306 to R.St-A.

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Authors and Affiliations

  1. Research Centre, Shriners Hospital for Children—Canada, 1003 Decarie Boulevard, Montreal, QC, H4A 0A9, Canada

    Hadla Hariri, Martin Pellicelli & René St-Arnaud

  2. Department of Human Genetics, McGill University, Montreal, QC, H3A 2T5, Canada

    Hadla Hariri & René St-Arnaud

  3. Departments of Surgery & Medicine, McGill University, Montreal, QC, H3A 2T5, Canada

    René St-Arnaud

  4. Research Institute, McGill University Health Centre, Montreal, QC, H4A 3J1, Canada

    René St-Arnaud

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  1. Hadla Hariri
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Correspondence to René St-Arnaud.

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Hadla Hariri, Martin Pellicelli, and René St-Arnaud declare no potential conflicts of interest.

Human and Animal Rights and Informed Consent

All reported studies/experiments with animal subjects performed by the authors have been previously published and complied with all applicable ethical standards (McGill University Institutional Animal Care and Use Committee and Canadian Council on Animal Care).

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This article is part of the Topical Collection on Molecular Biology of Skeletal Development

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Hariri, H., Pellicelli, M. & St-Arnaud, R. New PTH Signals Mediating Bone Anabolism. Curr Mol Bio Rep 3, 133–141 (2017). https://doi.org/10.1007/s40610-017-0060-z

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